Preemie Hypothermia for Neonatal Encephalopathy

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT01793129
First received: February 13, 2013
Last updated: August 13, 2014
Last verified: July 2014

February 13, 2013
August 13, 2014
October 2014
August 2017   (final data collection date for primary outcome measure)
Death or moderate or severe disability [ Time Frame: Birth to 18-22 months corrected age ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01793129 on ClinicalTrials.gov Archive Site
  • Number of deaths in the NICU and following discharge [ Time Frame: Birth to 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  • Differences in MRI findings after cessation of cooling/control obtained [ Time Frame: Birth to 40 weeks corrected age ] [ Designated as safety issue: Yes ]
  • Number of infants with moderate and severe disability [ Time Frame: Birth to 18-22 months corrrected age ] [ Designated as safety issue: Yes ]
  • Causes of Death [ Time Frame: Birth to 18-22 months corrrected age ] [ Designated as safety issue: Yes ]
    withdrawal of support and reasons for such will be tracked; attempts will be made to obtain autopsy whenever possible
  • Neurological injury by cranial ultrasound within 24 hours of enrollment [ Time Frame: Birth to 2 days of life ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Preemie Hypothermia for Neonatal Encephalopathy
A Randomized Trial of Targeted Temperature Management With Whole Body Hypothermia For Moderate And Severe Hypoxic-Ischemic Encephalopathy In Premature Infants 33-35 Weeks Gestational Age.

This study is a randomized, controlled trial to assess safety and effectiveness of whole body hypothermia for 72 hours in preterm infants 33-35 weeks gestational age (GA) who present at <6 hours postnatal age with moderate to severe neonatal encephalopathy (NE). The study will enroll infants with signs of NE at 18 NICHD Neonatal Research Network sites, and randomly assign them to either receive hypothermia or participate in a non-cooled control group.

Most clinical studies of neonatal encephalopathy (NE) and potential interventions have focused on infants ≥36 weeks GA. Although many interventions have been suggested and assessed for prevention or palliation of NE, the only one currently supported by rigorous clinical evidence to improve outcome in human newborns has been hypothermia implemented at <6 hours of postnatal age and maintained for 72 hrs. Data about diagnosis, frequency, severity, and outcome of NE in infants 33-35 weeks GA are sparse.

This trial will assess safety and effectiveness of whole body hypothermia for 72 hours in preterm infants 33-35 weeks gestational age (GA) who present at <6 hrs postnatal age with moderate to severe neonatal encephalopathy. Infants 33 0/7 to 35 6/7 weeks GA (best obstetrical estimate) and greater than or equal to 1500 grams birth weight (selected to minimize potential difficulties placing esophageal probe) who meet clinical, biochemical and neurologic criteria for moderate to severe NE will be randomized to either whole body hypothermia or participate in a non-cooled control group. The primary outcome will be death or moderate to severe disability at 18-22 months corrected age. The presence or absence of disability will be determined by the standard NRN interdisciplinary follow-up exam.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Infant, Newborn
  • Hypoxia, Brain
  • Hypoxia-Ischemia, Brain
  • Encephalopathy, Hypoxic-Ischemic
  • Hypoxic-Ischemic Encephalopathy
  • Ischemic-Hypoxic Encephalopathy
  • Device: Hypothermia
    Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours
  • Procedure: Normothermic Control
    Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
  • Experimental: Whole-body Hypothermia
    Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours
    Intervention: Device: Hypothermia
  • Placebo Comparator: Normothermia
    Control group (with esophageal temperature at or near 37.0°C) for 72 hours
    Intervention: Procedure: Normothermic Control
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
168
October 2019
August 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Infants 33 0/7 to 35 6/7 weeks GA (best obstetrical estimate)
  • Infants weight greater than or equal to 1500 grams at birth
  • Postnatal age less than 6 hours
  • Infants who meet clinical, biochemical and neurologic criteria for moderate to severe NE:

Biochemical: Cord gas or blood gas within first hour of life with pH ≤7.00 or base deficit (BD) ≥16 mEq/L OR

Acute perinatal event (e.g., abruptio placenta, cord prolapse, uterine rupture, severe FHR abnormality such as variable or late decelerations) AND Requirement for positive pressure ventilation for apnea or poor respiratory effort since birth for at least 10 minutes OR 10 minute Apgar score ≤5

AND

Neurologic:

Seizures OR modified Sarnat score with abnormalities in at least 3 of the 6 categories; at least one must be altered level of consciousness (lethargy or stupor/coma) as determined by a certified examiner (All infants who meet criteria for potential inclusion will undergo standard neurologic exam as for infants ≥36 wks GA being considered for hypothermia, with findings recorded)

Exclusion Criteria:

  • Receipt of sedative, analgesic or paralytic agent that may confound the qualifying neurologic exam
  • Etiology of NE not likely to be hypoxic-ischemic in origin
  • Major congenital anomaly that may confound outcome
  • Considered to be moribund and will not be receiving full intensive care
  • Equipment and/or appropriate staff not available
  • Core temperature < 33.5oC for more than one hour at time of screening
  • Unable to randomize by 6 hours of age
  • Infant needs ECMO
  • All blood gases (cord and postnatal at < 1hr of age) have a pH > 7.15 AND a base deficit < 10mEq/L
Both
33 Weeks to 35 Weeks
No
Contact: Roger G Faix, MD 801-581-7052
Contact: Rosemary D Higgins, MD 301-435-5575
United States
 
NCT01793129
NICHD-NRN-0051, U10HD021364, U10HD040689, U10HD021385, U10HD027851, U10HD027853, U10HD027856, U10HD027904, U10HD027880, U10HD034216, U10HD021373, U10HD040492, U10HD053109, U10HD040461, U10HD068244, U10HD068263, U10HD068270, U10HD068278, U10HD068284, U10HD036790
Yes
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Center for Research Resources (NCRR)
Principal Investigator: Michele C Walsh, MD Case Western Reserve University, Rainbow Babies and Children's Hospital
Principal Investigator: Seetha Shankaran, MD Wayne State University
Principal Investigator: Abbot R Laptook, MD Brown University, Women & Infants Hospital of Rhode Island
Principal Investigator: Ron N Goldbert, MD Duke University
Principal Investigator: Barbara J Stoll, MD Emory University
Principal Investigator: Brenda B Poindexter, MD, MS Indiana University
Principal Investigator: Abhik Das, PhD RTI International
Principal Investigator: Krisa P Van Meurs, MD Stanford University
Principal Investigator: Kurt Schibler, MD Cincinnati Children's Medical Center
Principal Investigator: Wally A Carlo, MD University of Alabama at Birmingham
Principal Investigator: Edward F Bell, MD University of Iowa
Principal Investigator: Kristi L Watterberg, MD University of New Mexico
Principal Investigator: Pablo J Sanchez, MD University of Texas Southwestern Medical Center at Dalla
Principal Investigator: Kathleen A Kennedy, MD, MPH The University of Texas Health Science Center, Houston
Principal Investigator: Barbara Schmidt, MD, MSc University of Pennsylvania
Principal Investigator: Carl T D'Angio, MD University of Rochester
Principal Investigator: Uday Devaskar, MD University of California, Los Angeles
Principal Investigator: Leif Nelin, MD Research Institute at Nationwide Children's Hospital
Principal Investigator: William Truog, MD Children's Mercy Hospital-Kansas City, MO
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP